Common DNA markers can account for more than half of the genetic influence on cognitive abilities

For nearly a century, twin and adoption studies have yielded substantial estimates of heritability for cognitive abilities, although it has proved difficult for genomewide-association studies to identify the genetic variants that account for this heritability (i.e., the missing-heritability problem). However, a new approach, genomewide complex-trait analysis (GCTA), forgoes the identification of individual variants to estimate the total heritability captured by common DNA markers on genotyping arrays. In the same sample of 3,154 pairs of 12-year-old twins, we directly compared twin-study heritability estimates for cognitive abilities (language, verbal, nonverbal, and general) with GCTA estimates captured by 1.7 million DNA markers. We found that DNA markers tagged by the array accounted for .66 of the estimated heritability, reaffirming that cognitive abilities are heritable. Larger sample sizes alone will be sufficient to identify many of the genetic variants that influence cognitive abilities

Protein kinase Cα (PKCα) regulates bone architecture and osteoblast activity.

Bones' strength is achieved and maintained through adaptation to load bearing. The role of the protein kinase PKCα in this process has not been previously reported. However, we observed a phenotype in the long bones of Prkca(-/-) female but not male mice, in which bone tissue progressively invades the medullary cavity in the mid-diaphysis. This bone deposition progresses with age and is prevented by disuse but unaffected by ovariectomy. Castration of male Prkca(-/-) but not WT mice results in the formation of small amounts of intramedullary bone. Osteoblast differentiation markers and Wnt target gene expression were up-regulated in osteoblast-like cells derived from cortical bone of female Prkca(-/-) mice compared with WT. Additionally, although osteoblastic cells derived from WT proliferate following exposure to estradiol or mechanical strain, those from Prkca(-/-) mice do not. Female Prkca(-/-) mice develop splenomegaly and reduced marrow GBA1 expression reminiscent of Gaucher disease, in which PKC involvement has been suggested previously. From these data, we infer that in female mice, PKCα normally serves to prevent endosteal bone formation stimulated by load bearing. This phenotype appears to be suppressed by testicular hormones in male Prkca(-/-) mice. Within osteoblastic cells, PKCα enhances proliferation and suppresses differentiation, and this regulation involves the Wnt pathway. These findings implicate PKCα as a target gene for therapeutic approaches in low bone mass conditions

The HAT TRICK programme for improving physical activity, healthy eating and connectedness among overweight, inactive men: study protocol of a pragmatic feasibility trial.

INTRODUCTION: Physical activity, healthy eating and maintaining a healthy weight are associated with reduced risk of cardiovascular disease, type 2 diabetes and cancer and with improved mental health. Despite these benefits, many men do not meet recommended physical activity guidelines and have poor eating behaviours. Many health promotion programmes hold little appeal to men and consequently fail to influence men's health practices. HAT TRICK was designed as a 12-week face-to-face, gender-sensitised intervention for overweight and inactive men focusing on physical activity, healthy eating and social connectedness and was delivered in collaboration with a major junior Canadian ice hockey team (age range 16-20 years). The programme was implemented and evaluated to assess its feasibility. This article describes the intervention design and study protocol of HAT TRICK. METHODS AND ANALYSIS: HAT TRICK participants (n=60) were men age 35 years, residing in the Okanagan Region of British Columbia, who accumulate 150 min of moderate to vigorous physical activity a week, with a body mass index of >25 kg/m2 and a pant waist size of >38'. Each 90 min weekly session included targeted health education and theory-guided behavioural change techniques, as well as a progressive (ie, an increase in duration and intensity) group physical activity component. Outcome measures were collected at baseline, 12 weeks and 9 months and included the following: objectively measured anthropometrics, blood pressure, heart rate, physical activity and sedentary behaviour, as well as self-reported physical activity, sedentary behaviour, diet, smoking, alcohol consumption, sleep habits, risk of depression, health-related quality of life and social connectedness. Programme feasibility data (eg, recruitment, satisfaction, adherence, content delivery) were assessed at 12 weeks via interviews and self-report. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of British Columbia Okanagan Behavioural Research Ethics Board (reference no H1600736). Study findings will be disseminated through academic meetings, peer-reviewed publication, web-based podcasts, social media, plain language summaries and co-delivered community presentations. TRIAL REGISTRATION NUMBER: ISRCTN43361357,Pre results

Expedited batch processing and analysis of transposon insertions

<p>Abstract</p> <p>Background</p> <p>With advances in sequencing technology, greater and greater amounts of eukaryotic genome data are becoming available. Often, large portions of these genomes consist of transposable elements, frequently accounting for 50% or more in vertebrates. Each transposable element family may have thousands or tens of thousands of individual copies within a given genome, and therefore it can take an exorbitant amount of time and effort to process data in a meaningful fashion.</p> <p>Findings</p> <p>In order to combat this problem, we developed a set of bioinformatics techniques and programs to streamline the analysis. This includes a unique Perl script which automates the process of taking BLAST, Repeatmasker and similar data to extract and manipulate the hit sequences from the genome. This script, called Process_hits uses an object-oriented methodology to compile all hit locations from a given file for processing, organize this data into useable categories, and output it in multiple formats.</p> <p>Conclusions</p> <p>The program proved capable of handling large amounts of transposon data in an efficient fashion. It is equipped with a number of useful sub-functions, each of which is contained within its own sub-module to allow for greater expandability and as a foundation for future program design.</p

Evaluation of NanoLuc, RedLuc and Luc2 as bioluminescent reporters in a cutaneous leishmaniasis model

New drugs for the treatment of human leishmaniasis are urgently needed, considering the limitations of current available options. However, pre-clinical evaluation of drug candidates for leishmaniasis is challenging. The use of luciferase-expressing parasites for parasite load detection is a potentially powerful tool to accelerate the drug discovery process. We have previously described the use of Leishmania amazonensis mutants expressing firefly luciferase (Luc2) for drug testing. Here, we describe three new mutant L. amazonensis lines that express different variants of luciferases: NanoLuc, NanoLuc-PEST and RedLuc. These mutants were evaluated in drug screening protocols. NanoLuc-parasites, in spite of high bioluminescence intensity in vitro, were shown to be inadequate in discriminating between live and dead parasites. Bioluminescence detection from intracellular amastigotes expressing NanoLuc-PEST, RedLuc or Luc2 proved more reliable than microscopy to determine parasite killing. Increased sensitivity was observed in vivo with RedLuc-expressing parasites as compared to NanoLuc-expressing L. amazonensis. Our data indicates that NanoLuc is not suitable for in vivo parasite burden determination. Additionally, RedLuc and the conventional luciferase Luc2 demonstrated equivalent sensitivity in an in vivo model of cutaneous leishmaniasis

Characterization of growth and metabolism of the haloalkaliphile Natronomonas pharaonis

Natronomonas pharaonis is an archaeon adapted to two extreme conditions: high salt concentration and alkaline pH. It has become one of the model organisms for the study of extremophilic life. Here, we present a genome-scale, manually curated metabolic reconstruction for the microorganism. The reconstruction itself represents a knowledge base of the haloalkaliphile's metabolism and, as such, would greatly assist further investigations on archaeal pathways. In addition, we experimentally determined several parameters relevant to growth, including a characterization of the biomass composition and a quantification of carbon and oxygen consumption. Using the metabolic reconstruction and the experimental data, we formulated a constraints-based model which we used to analyze the behavior of the archaeon when grown on a single carbon source. Results of the analysis include the finding that Natronomonas pharaonis, when grown aerobically on acetate, uses a carbon to oxygen consumption ratio that is theoretically near-optimal with respect to growth and energy production. This supports the hypothesis that, under simple conditions, the microorganism optimizes its metabolism with respect to the two objectives. We also found that the archaeon has a very low carbon efficiency of only about 35%. This inefficiency is probably due to a very low P/O ratio as well as to the other difficulties posed by its extreme environment

Linear Lattice and Trajectory Reconstruction and Correction at FAST Linear Accelerator

The low energy part of the FAST linear accelerator based on 1.3 GHz superconducting RF cavities was successfully commissioned. During commissioning, beam based model dependent methods were used to correct linear lattice and trajectory. Lattice correction algorithm is based on analysis of beam shape from profile monitors and trajectory responses to dipole correctors. Trajectory responses to field gradient variations in quadrupoles and phase variations in superconducting RF cavities were used to correct bunch offsets in quadrupoles and accelerating cavities relative to their magnetic axes. Details of used methods and experimental results are presented.Comment: 3 p

A Relational Event Approach to Modeling Behavioral Dynamics

This chapter provides an introduction to the analysis of relational event data (i.e., actions, interactions, or other events involving multiple actors that occur over time) within the R/statnet platform. We begin by reviewing the basics of relational event modeling, with an emphasis on models with piecewise constant hazards. We then discuss estimation for dyadic and more general relational event models using the relevent package, with an emphasis on hands-on applications of the methods and interpretation of results. Statnet is a collection of packages for the R statistical computing system that supports the representation, manipulation, visualization, modeling, simulation, and analysis of relational data. Statnet packages are contributed by a team of volunteer developers, and are made freely available under the GNU Public License. These packages are written for the R statistical computing environment, and can be used with any computing platform that supports R (including Windows, Linux, and Mac).